Nonradioactive sequence-specific oligonucleotide probes specific for the HLA-DP beta locus have been used in a simple dot-blot format to type samples amplified by the polymerase chain reaction from 44 patients with pauciarticular juvenile rheumatoid arthritis, 32 patients with adult rheumatoid arthritis, and 50 random controls. The sequences of four new DP beta alleles derived from these patients and controls are reported, bringing the total number of alleles identified thus far to 19. The DPB2.1 allele is significantly increased in juvenile rheumatoid arthritis patients over controls; this allele is not increased in patients with adult rheumatoid arthritis. The association of juvenile rheumatoid arthritis with the DPB2.1 allele is independent of linkage with previously defined HLA-D region markers of disease. Analysis of the DPB2.1 sequence shows that it differs from the nonsusceptible DPB4.2 allele by only 1 amino acid at position 69 in the beta 1 domain.